Review
Selective decontamination of the digestive tract reduces bacterial bloodstream infection and mortality in critically ill patients. Systematic review of randomized, controlled trials

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Summary

A systematic review and meta-analysis of randomized controlled trials (RCTs) of selective decontamination of the digestive tract (SDD) was undertaken to evaluate the impact of this procedure on bacterial bloodstream infection and mortality. Data sources were Medline, Embase, Cochrane Register of Controlled Trials, previous meta-analyses, and conference proceedings, without restriction of language or publication status. RCTs were retrieved that compared oropharyngeal and/or intestinal administration of antibiotics as part of the SDD protocol, with or without a parenteral component, with no treatment or placebo in the controls. The three outcome measures were patients with bloodstream infection, causative micro-organisms, and total mortality. Fifty-one RCTs conducted between 1987 and 2005, comprising 8065 critically ill patients were included in the review; 4079 patients received SDD and 3986 were controls. SDD significantly reduced overall bloodstream infections [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.59–0.90; P = 0.0036], Gram-negative bloodstream infections (OR, 0.39; 95% CI, 0.24–0.63; P < 0.001) and overall mortality (OR, 0.80; 95% CI, 0.69–0.94; P = 0.0064), without affecting Gram-positive bloodstream infections (OR, 1.06; 95% CI, 0.77–1.47). The subgroup analysis showed an even larger impact of SDD using parenteral and enteral antimicrobials on overall bloodstream infections, bloodstream infections due to Gram-negative bacteria and overall mortality with ORs of 0.63 (95% CI, 0.46–0.87; P = 0.005), 0.30 (95% CI, 0.16–0.56; P < 0.001), and 0.74 (95% CI, 0.61–0.91; P = 0.0034), respectively. Twenty patients need to be treated with SDD to prevent one Gram-negative bloodstream infection and 22 patients to prevent one death.

Introduction

Bloodstream infection (BSI) is the second most common infection in intensive care units (ICUs) after pneumonia.1 Pneumonia represents one third of all infections, whereas BSIs represent 15–20%.2, 3, 4 The attributable mortality is 35% (range 25–45%).5 Half of all BSI are due to Gram-positive bacteria, 40% are caused by aerobic Gram-negative bacilli (AGNB), and the remaining are polymicrobial or due to yeasts.5, 6, 7, 8 Potentially pathogenic micro-organisms carried by the critically ill in the oropharynx are the most important sources of bacteria causing pneumonia.9 Micro-organisms infecting the lungs10 and bladder,11 and carried in the gut can invade the bloodstream.12

Selective decontamination of the digestive tract (SDD) is an infection control strategy mainly targeting AGNB. SDD includes a parenteral component, usually cefotaxime, given for a few days on admission, and enteral polymyxin, tobramycin, amphotericin B (PTA) throughout the treatment in ICU.13 Eleven meta-analyses of randomized, controlled trials (RCTs) of SDD have been published.2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 The majority assessed the impact of SDD on pneumonia and mortality, whereas only three meta-analyses with the endpoint of BSI showed a significant reduction in BSI in patients receiving SDD.18, 20, 21 However, these reviews have important limitations, e.g. small number of RCTs, inclusion of non-randomized studies, and the use of infection episodes rather than patients. In a recent meta-analysis, evaluating the impact of the antifungal component of SDD on fungal carriage and infection, overall fungal infections but not fungaemia were significantly reduced by SDD.23

A systematic review and meta-analysis of RCTs was undertaken to test whether SDD reduces the number of patients with BSI due to bacteria, what types of causative micro-organisms causing BSI were affected by SDD, and total mortality in patients with BSIs.

Section snippets

Identification of relevant literature and retrieval of studies

The following databases were searched: Medline (January 1976 to June 2005), Embase (January 1980 to June 2005), and the Cochrane Register of Controlled Trials (June 2005), using the search terms: ‘intensive care unit’, ‘critical care’, ‘antibiotic combined therapeutic use’, ‘antibiotic combined administration and dosages’, ‘decontamination’, ‘respiratory tract infection prevention and control’, ‘bacterial infection’, ‘septicaemia’, ‘bacteraemia’, ‘sepsis’, with the keywords ‘SDD’, ‘selective

Overall search findings

We evaluated 123 potentially eligible clinical trials (Figure 1). Of these trials, 68 were excluded: 47 because they were not randomized, 18 due to double publication or because they included data extracted from the main publication, and three because both patients and controls received SDD. We identified 55 potentially appropriate RCTs. Moreover, four randomized trials were excluded because the endpoint was mortality and endotoxaemia rather than infection.27, 28, 29, 30 A final sample of 51

Discussion

Four important findings emerge from this review. First, SDD using parenteral and enteral antimicrobials significantly reduced overall BSIs by 37%. Second, there were significantly less patients with BSI due to AGNB in the group receiving SDD. Third, the number of patients with Gram-positive BSIs was similar in the test and control groups. Fourth, in patients with BSI, the full SDD protocol significantly reduced the odds ratio for mortality to 0.74 (95% CI 0.60–0.91) with an absolute mortality

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